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EP1560641B1 - Procede de preparation d'emulsions - Google Patents

Procede de preparation d'emulsions Download PDF

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Publication number
EP1560641B1
EP1560641B1 EP03776682A EP03776682A EP1560641B1 EP 1560641 B1 EP1560641 B1 EP 1560641B1 EP 03776682 A EP03776682 A EP 03776682A EP 03776682 A EP03776682 A EP 03776682A EP 1560641 B1 EP1560641 B1 EP 1560641B1
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EP
European Patent Office
Prior art keywords
emulsion
emulsification method
magnetic field
emulsification
liquids
Prior art date
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EP03776682A
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German (de)
English (en)
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EP1560641A1 (fr
Inventor
Jan Nuyens
Johan Martens
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Katholieke Universiteit Leuven
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Katholieke Universiteit Leuven
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Priority claimed from GB0226503A external-priority patent/GB0226503D0/en
Priority claimed from GB0304356A external-priority patent/GB0304356D0/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40—Mixing liquids with liquids; Emulsifying
    • B01F23/41—Emulsifying
    • B01F23/411—Emulsifying using electrical or magnetic fields, heat or vibrations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/451—Magnetic mixers; Mixers with magnetically driven stirrers wherein the mixture is directly exposed to an electromagnetic field without use of a stirrer, e.g. for material comprising ferromagnetic particles or for molten metal
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J19/087—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor employing electric or magnetic energy
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
    • B01F25/50—Circulation mixers, e.g. wherein at least part of the mixture is discharged from and reintroduced into a receptacle
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/08—Processes employing the direct application of electric or wave energy, or particle radiation; Apparatus therefor
    • B01J2219/0873—Materials to be treated
    • B01J2219/0881—Two or more materials
    • B01J2219/0888—Liquid-liquid

Definitions

  • the present invention is in the field of the manufacture of emulsions.
  • the invention is in the field of preparing stable oil-in-water and water-in-oil emulsions. More specifically, the invention relates to a method and a system for the preparation of stable emulsions by conducting an unstable pre-mixture of immiscible fluids, optionally containing solid particles, through one or more magnetic fields.
  • Emulsions may be broadly defined as metastable colloidal dispersions of liquid droplets in another liquid phase.
  • emulsions are disperse systems comprising at least two liquids which are virtually insoluble in one another.
  • the formation of an emulsion requires energy and occurs at conditions far from equilibrium.
  • the formation of an emulsion comprises the two following steps:
  • Emulsions may either be produced directly as consumer products or as intermediates for use within a broad range of industrial applications including, in a far from exclusive list, food, paints, cosmetics, pharmaceuticals, explosives, rocket fuel, lubricants, foam-controlling agents, etc.
  • Most industrial applications or consumer products require that emulsions have maximal storage stability.
  • the storage stability refers to the period of time during which the emulsion can be kept before it separates again into different phases.
  • Mechanisms that can be identified in the process of breaking down an emulsion include the so-called Ostwald ripening, creaming, aggregation, coalescence, and partial coalescence.
  • the process of breaking down an emulsion can be influenced or monitored, and therefore storage stability can be controlled or increased, in the two following ways: using mechanical devices to control the size of the dispersed droplets and/or adding stabilising chemical additives or emulsifiers in order to keep the emulsion dispersed.
  • Emulsions have great importance in the plastics (i.e. polymers) industry, especially in the detergents and cleaning products industries, in the production of lubricants, cosmetic, veterinary or pharmaceutical compositions (e.g. creams and ointments) and, in particular, in food products technology as well. Since many emulsions comprise at least one hydrophilic liquid and at least one lipophilic liquid, a further distinction is usually made, depending on the nature of the internal, disperse phase, between oil-in-water emulsions and water-in-oil emulsions.
  • the internal or the external phase of the emulsion may itself in turn be a disperse system and may, for example, include particles of solids dispersed in the respective liquid phase, a system of this kind being also referred to as a multiphase emulsion.
  • emulsions Owing to the interfacial tension which exists between the droplets of the internal phase and the droplets of the continuous, external phase, emulsions are in general thermodynamically unstable and thus after some time a phase separation occurs which may be induced, for example, by droplet sedimentation or coagulation.
  • emulsifying auxiliaries such as emulsifiers (which lower the interfacial tension) or stabilisers (which, for instance, prevent or at least greatly retard the sedimentation of the droplets, by increasing the viscosity of the continuous, external phase).
  • the initial result is a coarsely disperse crude emulsion.
  • the large drops of the crude emulsion are broken up and the desired fine emulsion is formed.
  • the smallest droplet size achievable in the last step of the emulsification process depends not only on the respective input of power in the emulsifying equipment but can be also critically influenced by the nature and concentration of the emulsifying auxiliaries. For example, in order to produce ultra-thin emulsions, it is essential that the new interfaces which are formed mechanically be occupied very rapidly by the emulsifier in order to prevent coalescence of the droplets.
  • the average size of the droplets of the disperse phase can be determined in accordance with the principle of quasi-elastic dynamic light scattering, for instance by using a Coulter N4+ particle analyser commercially available from Coulter Scientific Instruments.
  • Emulsions of medium to high viscosity are produced mainly by means of rotor-stator systems, such as colloid mills or gear-rim dispersing machines.
  • Low-viscosity emulsions have to date been produced mainly using high-pressure homogenizers, in which case the crude emulsion under a pressure of between about 100 bars and 1,000 bars is discharged through the about 10 to 200 ⁇ m high radial gap of a homogenizing nozzle. It is assumed that drop break-up in this case is mainly attributable to the effect of cavitation.
  • high-pressure homogenizer is the microfluidizer, which operates at relatively low pressures of about 100 bars.
  • high-pressure homogenizers are not without disadvantages. Especially when emulsifying polymerizable systems or when producing multiphase emulsions including solid particles, the narrow radial gap of the homogenizing nozzle may easily become clogged. The subsequently required cleaning is time-consuming and complex.
  • the high pressures used in this type of equipment entail, sealing problems, especially when using liquid components which attack the equipment sealants.
  • a further disadvantage of high-pressure homogenizers is that drop size and throughput are closely linked with each other. Such equipment is therefore unsuitable for producing emulsions in whose disperse phase it is intended to disperse solid particles.
  • Liposomes may be defined as vesicles in which an aqueous volume is entirely enclosed by a bilayer membrane composed of lipid molecules. When dispersing these lipids in aqueous media, a population of liposomes with sizes ranging from about 15 nm to about 1 ⁇ m may be formed.
  • the three major types of lipids i.e. phospholipids, cholesterol and glycolipids, are amphipathic molecules which, when surrounded on all sides by an aqueous environment, tend to arrange in such a way that the hydrophobic "tail” regions orient toward the center of the vesicle while the hydrophilic "head” regions are exposed to the aqueous phase. According to this mechanism liposomes thus usually form bilayers.
  • liposomes are known in the art.
  • MLV multilamellar vesicles
  • aqueous layer usually having a size between about 100 nm and 1 ⁇ m, which known e.g. from U.S. Patent No. 4,522,803 and U.S. Patent No. 4,558,579.
  • Their production can be reproducibly scaled-up to large volumes and they are mechanically stable upon storage for long periods of time.
  • SUV small unilamellar vesicles
  • SUV small unilamellar vesicles
  • the curvature of the membrane increases in SUV, it develops a degree of asymmetry, i.e. the restriction in packing geometry dictates that significantly more than 50% and up to 70% of the lipids making up the bilayer are located on the outside.
  • liposomes may be made from neutral phospholipids, negatively-charged (acidic) phospholipids, sterols and other non-structural lipophilic compounds.
  • a population of detergent-free liposomes having a substantially monomodal distribution i.e. unilamellar vesicles
  • a mean diameter greater than 50 nm and exhibiting less than a two-fold variation in size may be produced (e.g. according to EP-B-185,756) by first preparing multilamellar liposomes and then repeatedly passing them under pressure through a filter having a pore size not more than 100 nm.
  • Liposome manufacturing and quality control encounters many of the difficulties set forth herein-above in respect of other dispersed systems including multiphase emulsions.
  • the said pre-mix may further comprise one or more emulsifiers or emulsion stabilizers.
  • a system for the preparation of an emulsion according to the method of the invention comprises means for generating one or more magnetic fields, such as a magnetic fluid conditioner, the said means being mounted in a circuit or loop comprising at least a liquid containing portion, i.e. a reservoir or container, filled with two or more originally immiscible liquids, the said system further comprising means whereby the two or more liquids contained in the liquid containing portion can be conducted or circulated through the said one or more magnetic fields being for instance generated by the magnetic fluid conditioner.
  • a mixer may be mounted on the liquid containing portion of the emulsification system for stirring the two or more liquids contained therein.
  • the circuit or loop includes one or more tubings, channels or ducts wherein the two or more liquids can flow from and back to the liquid containing portion, and the means for circulating the two or more liquids through the magnetic field(s) includes one or more pumps mounted in the said circuit or loop.
  • the said pump(s) may be designed or operated such as to allow for controlling or regulating, e.g. keeping constant or else varying according to a predetermined scheme, the speed at which the two or more liquids are conducted or circulated through the magnetic field(s).
  • the two or more liquids may be re-circulated one or more times through the magnetic field(s) back into the liquid containing portion of the system, for instance until an emulsion with suitable characteristics (e.g. droplet or micelle average size or size distribution) is obtained.
  • pre-mixing of the two or more immiscible liquids may be carried out or conducted through a magnetic field before transferring the resulting pre-mix to the liquid containing portion of the above-mentioned system.
  • the method of the invention may be carried out continuously or intermittently, the latter meaning with storage of the emulsion in the liquid containing portion of the emulsification system of the present invention after and before conducting or circulating the said emulsion through the one or more magnetic field(s). Intermittent circulation through the magnetic field may, for certain emulsions of two or more liquids, allow improving the storage stability of the said emulsions.
  • the present invention relates to the unexpected finding that circulating an unstable mixture of immiscible liquids through a magnetic field under suitable conditions, such as magnetic field strength, temperature, number of re-circulation times and the like, results in a stable emulsion. Furthermore, various operational parameters of this method were identified as relevant to the efficiency of preparation of a stable emulsion and to the stability of the said emulsion. The influence of some of these parameters is detailed herein-after and illustrated in the following examples.
  • a first embodiment of this invention relates to a method for preparing emulsions of two or more immiscible liquids by flowing, conducting or circulating one or more times a pre-mix of said liquids, optionally having solid particles suspended therein, through one or more magnetic fields.
  • the present invention also provides the use of equipment for performing the method, i.e. an emulsification system comprising two or more immiscible liquids, means for generating one or more magnetic fields, and means for flowing or circulating said fluid one or more times through the said one or more magnetic fields.
  • a means for measuring the average size or size distribution of the emulsion droplets or micelles may also be provided as a further component of the emulsification system of the invention.
  • the number of immiscible liquids is not a critical parameter of the present invention.
  • the presence of both at least a hydrophilic liquid, for instance an aqueous or nearly-aqueous phase, and at least a lipophilic (or hydrophobic) liquid is preferred.
  • the chemical nature, molecular size or other physical characteristic of the lipophilic (or hydrophobic) liquid is not critical.
  • Such lipophilic liquids include, without limitation, edible oils (e.g.
  • fatty acids and esters thereof including esters formed from a saturated or unsaturated linear or branched aliphatic alcohol having from 1 to 18 carbon atoms, in particular methyl or ethyl esters, or from a saturated or unsaturated linear or branched aliphatic polyol having from 2 to 6 carbon atoms, in particular glycerol, trimethylolpropane, sorbitan, sorbitol, pentaerythritol, neopentyl glycol and mixtures thereof, or from a polyethyleneglycol or polypropyleneglycol or methoxy polyethyleneglycol having a molecular weight up to 1,500), preferably natural or synthetic, saturated, mono-unsaturated or polyunsaturated acids having from 8 to 24 carbon atoms and optionally one or more functional groups such as hydroxy or epoxy such as caprylic, capric, lauric, myr
  • the effect of the method of the invention on the average size of droplets or micelles of the emulsion is more important when the strength of the magnetic field is higher and/or the number of re-circulations through the magnetic field is higher.
  • a means to increase the effective magnetic field is to flow the suspension through a number of magnets arranged in series (especially for limiting or prolonging the duration of treatment) and/or to re-circulate the suspension several times, i.e. preferably at least 10 times, more preferably at least 40 times, through the same magnetic field.
  • the strength of each said magnetic field used for carrying out the method of the invention is at least about 2,000 gauss at the active region thereof.
  • flowing the premix of said liquids through the magnetic field(s) is preferably effected at a temperature below the Curie temperature of the magnetic material used for generating said magnetic field(s), e.g. below about 400°C for a magnetic device of the Al-Ni-Co type.
  • Flowing the pre-mix of said liquids through said magnetic field(s) is also preferably effected at a temperature between the freezing or solidifying temperature and the boiling temperature of said pre-mix under the pressure prevailing while flowing said pre-mix of liquids through said magnetic field(s).
  • flowing said pre-mix of immiscible liquids through said magnetic freld(s) is preferably effected at a temperature between about 10°C and about 90°C, for practical and economical reasons more preferably between about 18°C and about 70°C.
  • the respective proportions of the immiscible liquids in the pre-mix to be magnetically treated is not a critical parameter of this invention and may be adapted, using standard practice in the art, depending upon the consumer product or industrial application which is targeted for the relevant emulsion.
  • the proportion of the lipophilic liquid(s) in the pre-mix may be within a range from about 3 to about 60% by weight, preferably from 5 to 40% by weight, more preferably from 10 to 35% by weight, depending upon the exact nature of the said lipophilic liquid(s) and the optional emulsifiers.
  • emulsifiers or surfactants of any class well known in the art, e.g. anionic surfactants, non-ionic surfactants or cationic surfactants.
  • suitable emulsifiers and the desirable amount thereof, depending upon the exact nature and amount of the said lipophilic liquid(s), are within the knowledge of those of ordinary skill in the art.
  • Suitable emulsifiers or surface-active agents include water-soluble natural soaps and water-soluble synthetic surface-active agents.
  • Suitable soaps include alkaline or alkaline-earth metal salts, unsubstituted or substituted ammonium salts of higher fatty acids (C 10 -C 22 ), e.g. the sodium or potassium salts of oleic or stearic acid, or of natural fatty acid mixtures obtainable form coconut oil or tallow oil.
  • Synthetic surface-active agents include anionic, cationic and non-ionic surfactants, e.g.
  • sodium or calcium salts of polyacrylic acid sulphonated benzimidazole derivatives preferably containing 8 to 22 carbon atoms; alkylarylsulphonates; and fatty sulphonates or sulphates, usually in the form of alkaline or alkaline-earth metal salts, unsubstituted ammonium salts or ammonium salts substituted with an alkyl or acyl radical having from 8 to 22 carbon atoms, e.g.
  • alkylarylsulphonates are the sodium, calcium or alcanolamine salts of dodecylbenzene sulphonic acid or dibutyl-naphtalenesulphonic acid or a naphtalene-sulphonic acid/formaldehyde condensation product.
  • corresponding phosphates e.g. salts of phosphoric acid ester and an adduct of p-nonylphenol with ethylene and/or propylene oxide
  • Suitable emulsifiers further include partial esters of fatty acids (e.g. lauric, palmitic, stearic or oleic) or hexitol anhydrides (e.g., hexitans and hexides) derived from sorbitol, such as commercially available polysorbates.
  • partial esters of fatty acids e.g. lauric, palmitic, stearic or oleic
  • hexitol anhydrides e.g., hexitans and hexides
  • Other emulsifiers which may be employed include, but are not limited to, materials derived from adding polyoxyethylene chains to non-esterified hydroxyl groups of the above partial esters, such as Tween 60 commercially available from ICI Americas Inc.; and the poly(oxyethylene) poly(oxypropylene) materials marketed by BASF under the trade name Pluronic.
  • the method according to the invention involves re-circulating two or more times the liquids through the magnetic field(s).
  • the number of re-circulation times may be quite high, e.g. up to 10,000 times through one magnetic field, preferably up to 3,000 times through one magnetic field, and may be easily adapted to the specific average size targeted for the droplets or micelles of an emulsion designed for a certain industrial or consumer product application. It is important that the liquids are flowed or circulated through the magnetic field(s) at a speed which allows the magnetic treatment to effectively perform droplet or micelle formation to a significant extent within a specified period of time.
  • the linear flow rate of said liquids through each said magnetic field is between 0.25 and 25 m/s, more preferably between 0.6 and 5 m/s.
  • the residence time of said liquids through each said magnetic field is preferably between 60 microseconds and 10 seconds, depending upon the number or re-circulation times.
  • the present invention also provides an industrial process which, in addition to including the above described emulsification method as a process step, may further comprise one or more post-processing steps.
  • Said post-processing step may be a heating step or, especially for improving the stability of the resulting emulsion, a cooling step preferably to a temperature below room temperature, more preferably to a temperature within a range from about 2°C to about 8°C. It is usually advantageous to perform said cooling step until the moment when the emulsion is to be effectively used in the relevant final application.
  • said post-processing step may be a drying step, which can be performed by any known drying technique, for at least partly removing the hydrophilic liquid from the emulsion.
  • said post-processing step may be a freeze-drying step suitable for handling and storing the liposomes formed in the solid state.
  • the post-processing step may be a step of diluting the emulsion through the addition of a hydrophilic liquid, preferably the same as originally used, into said emulsion.
  • the post-processing step may be a sonication step.
  • the industrial process of the invention may further comprise one or more steps of controlling the size of droplets or micelles produced during the emulsification method.
  • said size controlling step is preferably performed by dynamic light scattering analysis.
  • said industrial process comprises a post-processing step performed following the emulsification step, it may further comprise one or more steps of controlling the size of droplets or micelles produced during or after said post-processing step, in which case said size controlling step after said post-processing step may be performed by dynamic light scattering analysis.
  • the size controlling step may be performed in such a way as to measure the average size and/or the size distribution of the droplets or micelles produced during the various steps of said industrial process.
  • the present invention also provides products having adequate or improved storage stability, such as detergents, cleaning products, lubricants, cosmetic, veterinary and pharmaceutical compositions (e.g. creams and ointments) and food products, including an emulsion prepared according to the method described herein-above.
  • products having adequate or improved storage stability such as detergents, cleaning products, lubricants, cosmetic, veterinary and pharmaceutical compositions (e.g. creams and ointments) and food products, including an emulsion prepared according to the method described herein-above.
  • the present invention shows a number of advantages over the methods of the prior art. It achieves a substantial simplification in terms of equipment and maintenance costs associated with the equipment required for emulsification. It allows for easy access to and efficient control of the desired emulsion characteristics (including, but not limited to, micelle size) and emulsion storage stability, whatever the nature of the lipophilic phase and its proportion in the emulsion. Thirdly, it is widely applicable to all kinds of emulsions, including oil-in-water and water-in-oil emulsions, as well as to the manufacturing of all kinds of liposomes.
  • the hot suspension was then magnetically treated in an emulsification system schematically shown in figure 1A and which may be described as follows.
  • the system comprises a tubing (1); two external magnetic devices (2) arranged in series, commercially available from CEPI-CO (Antwerp, Belgium) under the trade name CEPI-SAN R1/2D and providing a strength of about 10,000 gauss, the said magnetic devices being mounted so as to create two consecutive orthogonal magnetic fields inside the fluid passing through; a pump (4) commercially available from Thermo Electron GmbH, Düsseldorf, Germany under the trade name Haake D8 and disposed inside a reservoir (5) being a so-called Haake circulation bath for receiving the suspension.
  • the tubing (1) was attached to the pump (4) in such a way that the magnetic device (2) was in a downstream direction.
  • the hot suspension was poured into the reservoir (5), while mechanical stirring was immediately started by means of the IKA RE16 mixer (not shown in figure 1A) operated at 200 rpm.
  • the suspension was pumped through pump (4) at a speed of about 3 I/minute through the magnetic devices (2), and such treatment was continued for 360 minutes, while allowing the suspension to cool spontaneously.
  • Sample s0 was separating quickly into a white yellow top layer and a white water layer. Each of emulsion samples s1-4 appeared by eye to be stable after 6 hours. After overnight storage at room temperature, most of the emulsion samples s1-4 showed some phase separation, although less significant when a longer magnetic treatment was continued (i.e. sample s4).
  • a first step 1.163 kg of the same fatty acid and 0.076 kg of the same surfactant as used in example 1 were added to 2.5 kg of de-ionised water.
  • the resulting pre-mix was vigorously stirred with an IKA RE16 mixer at 300 rpm.
  • the suspension was then slowly heated to a temperature of 63 °C with an IKA RCT heater. Temperature was controlled with an IKA ETS-D4 apparatus. After temperature has reached 60.5°C, 14.62 g of a 50 % by weight NaOH solution was added dropwise to the suspension, while continuing stirring of the mixture. The suspension was then allowed to cool to 40°C.
  • a second step 1.5 I of the suspension (still at a temperature of 40°C) was poured into the liquid containing portion (5), having a 2 l volume, of the emulsification system shown in figure 1 B.
  • Said liquid containing portion (5) consists of a cylindrical flask with a conic bottom to which a tubing (1a) (commercially available under the trade name Masterflex Tygon lab I/P 70 from Cole-Parmer Instrument Company).
  • the pump (4) commercially available from Cole-Parmer Instrument Company under the trade name Masterflex I/P
  • the suspension was pumped through tubing (1b) to the top of the flask (5).
  • a commercial magnetic device (2) commercially available from CEPI-CO (Antwerp, Belgium) under the trade name CEPI-SAN R1/4D was attached to the end of the tubing (1b) at the inlet of the liquid containing portion (5).
  • the pump (4) was continuously operated at a speed of 4.7 I/minute for 60 minutes.
  • a fatty acid aqueous suspension was made exactly as in the first step of example 2. After further spontaneous cooling down and storing for 5 days at room temperature (about 20°C), the batch of the pre-mixed suspension was stirred once more (by means of IKA RE16 operated at 300 rpm) but not heated. Part of the batch was used for a blank experiment as explained below.
  • Said liquid containing portion (5) consists of a cylindrical flask with a conic bottom.
  • a commercial magnetic device (2) (same as used in example 2) is mounted in a loop at the outlet of the liquid containing portion (5), except during the blank experiment.
  • the loop consists of a tubing (1a, 1b) (same type as used in example 2) which connects the magnetic device (2) to the inlet on top of the flask (5) via a pump (4) (same as used in example 2).
  • the said pump was continuously operated at a speed of 4.7 l/minute.
  • samples b2, b'2, b3 and b'3 showed phase separation within 20 hours after treatment. This demonstrates that conducting an emulsion through a magnetic field under the above experimental conditions significantly contributes to the formation of a stable emulsion.
  • a fatty acid aqueous suspension was made exactly as in the first step of example 2. After further spontaneous cooling down and storing for 11 days at room temperature (about 20°C), the batch of the pre-mixed suspension was stirred once more (by means of IKA RE16 operated at 300 rpm) but not heated. Part of the batch was used for a blank experiment as explained below.
  • a fatty acid aqueous suspension was made exactly as in the first step of example 2.
  • a second step 1.5 I of the suspension (still at a temperature of 40°C) was poured into the liquid containing portion (5), having a 2 I volume, of the emulsification system shown in figure 1C, the pump (4) being continuously operated at a speed of 4.7 I/minute.
  • the emulsion was pumped through the magnetic device into a 1 litre glass Erlenmeyer where the sample was collected and stored at room temperature for further stability determination by visual inspection.
  • the sample was found to be stable for more than 19 days, i.e. significantly more than the samples of example 3 being manufactured under the same conditions but stored in small glass vials.
  • the emulsification system used is shown in figure 1D and comprises a cylindrical flask (5) with a conic bottom which is used as a liquid containing portion.
  • the tubing (1a, 1b) connects the magnetic device (2) via the pump (4) (Masterflex I/P) with the inlet on top of the flask (5).
  • the whole system is positioned in a box (6) filled with a mixture of water and ice.
  • the magnetic device (2), part of the tubing (1a) and part of the flask (5) are immersed in the said mixture. This setup allows cooling milk at a temperature below 20 °C.
  • pump (4) is turned on and continuously operated at a flow rate of 4.7 I/minute, i.e. a linear velocity of 1.1 m/s. Before treatment, and after 5 minutes and 10 minutes of magnetic treatment respectively, samples were taken in the flask (5) for further analysis.
  • the size of fat micelles present in milk were analysed with diffusive light scattering, using a high performance particle sizer with a He-Ne-Laser (2,5 mW) from ALV Company. Measurements were performed with water as standard reference for viscosity, and without making a correction for viscosity, therefore micelles sizes should be interpreted as relative rather than absolute values, as shown in figure 2.
  • Example 8 magnetic treatment of a dodecane water-in-oil emulsion
  • This emulsion was magnetically treated in the emulsification system shown in figure 4 and comprising, within a loop, a tubing (1) (Masterflex Tygon lab I/P 70 from Cole Parmer Instrument Company), a magnetic device (2) of the Al-Ni-Co type and providing a strength of about 10,000 gauss (same as used in example 2) and a 3-way horizontal ball valve (3) (commercially available from Georg Fischer Rohr Oberssysteme AG under the trade name 343 DN10/15).
  • the tubing (1) was attached to a pump (4) (Masterflex I/P) in such a way the magnetic device (2) was in a downstream direction.
  • the total volume of this system is 0,100 I. Part of the system is placed in a box (6) cooled with a mixture of water and ice.
  • the emulsion temperature is kept below room temperature during treatment.
  • the emulsion was magnetically treated during 20 minutes while applying a pumping speed of 4.7 I/minute (corresponding to a linear flow rate of 1.1 m/s).
  • the magnetically treated emulsion was sampled at room temperature, the sample (s2) was inspected visually and compared to the corresponding sample (s1) taken before treatment, both samples being collected and kept in a 120 ml glass bottle.
  • Sample s1 shows phase separation within 2 hours, including a transparent watery top layer.
  • Sample s2 was still stable after 94 hours, its phase separation occurring only after 118 hours.
  • This emulsion was magnetically treated in the emulsification system shown in figure 4 at the same pumping speed of 4.7 I/minute.
  • the magnetically treated emulsion was sampled at room temperature, the sample (s2) was inspected visually and compared to the corresponding sample (s1) taken before treatment. Improvement in storage stability was significant, since s1 showed phase separation only 5 minutes after preparation, whereas s2 was still stable after 3 hours storage at room temperature and showed de-mixing only after 13.5 hours storage.
  • Sample s2 was also analysed by diffusive light scattering under the same conditions as in example 6.
  • Figure 5 shows the micelle size distribution of sample s2 in the range from 30 nm to 100,000 nm.
  • Example 10 magnetic treatment of a 60% soybean oil emulsion
  • This emulsion was magnetically treated in the emulsification system shown in figure 4 at the same pumping speed of 4.7 I/minute.
  • the magnetically treated emulsion was sampled at room temperature, the sample (s4) was inspected visually and compared to the corresponding sample (s3) taken before treatment. Improvement in storage stability was significant, since s3 showed phase separation only 60 minutes after preparation, whereas s4 was still stable after 18 hours storage at room temperature and showed de-mixing only after 109 hours storage.
  • Sample s4 was also analysed by diffusive light scattering under the same conditions as in example 6.
  • Figure 6 shows the micelle size distribution of sample s4 in the range from 10 nm to 100,000 nm.
  • a fatty acid aqueous suspension was made exactly as in the first step of example 2.
  • the said suspension (still at a temperature of 40°C) was treated in the emulsification system shown in figure 4, the pump (4) being continuously operated at a speed of 1.7 I/minute (corresponding to a linear flow rate of 0.4 m/s).
  • sample s'2 with a time indication 0', indicates a sample taken shortly after pouring the emulsion into the tubing system (in doing so, the pump was turned on a few times, meaning the liquid had yet passed through the magnetic device a few times).
  • Table 5 time (min) sample room temp sample refrigerator DLS 0 s1 s'1 0' s'2 15 s'3 30 s'4 s"4 60 s5 s'5 s"5
  • Samples s1 and s'1 separated quickly into a white yellow top layer and a white water layer. Sample s'2 separated similarly 4hours later. Sample s'3 was de-mixed after 14 hours. Samples s'4, s5 and s'5 remained homogeneous for at least 72 hours but were de-mixed after 138 hours.
  • Figure 7 shows the distribution of relative masses of the micelles (in the range from 10 nm to 2,000 nm) of samples s"4 and s"5 obtained after 30 minutes and 60 minutes treatment respectively. This clearly shows a narrowing of the distribution around an average size of about 150 nm upon prolonged magnetic treatment for 1 hour.

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Claims (17)

  1. Procédé d'émulsification comprenant l'écoulement, la conduite ou la mise en circulation d'un prémélange de deux ou plusieurs liquides non miscibles à travers un ou plusieurs champs magnétiques sous des conditions pour émulsionner ledit prémélange, dans lequel ledit prémélange de deux ou plusieurs liquides non miscibles est du lait ou comprend au moins un liquide hydrophile et au moins un liquide lipophile, dans lequel ledit liquide lipophile est sélectionné à partir du groupe constitué d'huiles comestibles, de graisses, d'acides gras et d'esters de ces derniers formés à partir d'un alcool aliphatique linéaire ou ramifié saturé ou non saturé ayant de 1 à 18 atomes de carbone ou à partir d'un alcool polyvalent aliphatique linéaire ou ramifié saturé ou non saturé ayant de 2 à 6 atomes de carbone ou à partir d'un polyéthylène glycol ou d'un polypropylène glycol ou d'un méthoxy polyéthylène glycol ayant un poids moléculaire allant jusqu'à 1 500 ; d'acides naturels ou synthétiques, saturés, mono-insaturés ou polyinsaturés ayant de 8 à 24 atomes de carbone et de manière facultative un ou plusieurs groupes fonctionnels comme l'hydroxy ou l'époxy ; des lipides incluant les mono- et polyacylglycérols, des phosphoglycérides, des sphingolipides, des amino-amidines, et des mélanges de ces derniers, et dans lequel le débit linéaire desdits liquides à travers chaque dit champ magnétique est compris entre 0,25 et 25 m/s.
  2. Procédé d'émulsification selon la revendication 1, dans lequel ledit liquide hydrophile est une phase aqueuse ou presque aqueuse.
  3. Procédé d'émulsification selon la revendication 1 ou la revendication 2, dans lequel ledit prémélange comprend de plus un ou plusieurs régulateurs de viscosité et/ou un ou plusieurs émulsifiants ou des stabilisateurs d'émulsion ou des agents de surface.
  4. Procédé d'émulsification selon l'une quelconque des revendications 1 à 3, dans lequel ledit prémélange comprend de plus des particules solides suspendues en son sein.
  5. Procédé d'émulsification selon l'une quelconque des revendications 1 à 4, dans lequel l'intensité de chaque dit champ magnétique est d'au moins 2 000 gauss.
  6. Procédé d'émulsification selon la revendication 2, dans lequel la proportion dudit liquide lipophile dans ledit prémélange est dans une plage de 3 à 60 % en poids.
  7. Procédé d'émulsification selon l'une quelconque des revendications 1 à 6, dans lequel ledit prémélange de deux ou plusieurs liquides non miscibles est remis en circulation de 10 à 10 000 fois à travers chaque dit champ magnétique.
  8. Procédé d'émulsification selon l'une quelconque des revendications 1 à 7, dans lequel le débit linéaire desdits liquides à travers chaque dit champ magnétique est compris entre 0,6 et 5 m/s.
  9. Procédé d'émulsification selon l'une quelconque des revendications 1 à 8, dans lequel le temps de résidence dudit fluide à travers chaque dit champ magnétique est compris entre 60 microsecondes et 10 secondes.
  10. Procédé d'émulsification selon l'une quelconque des revendications 1 à 9, dans lequel l'écoulement desdits liquides à travers le(s)dit(s) champ(s) magnétique(s) est effectué à une température comprise entre 10 °C et 90 °C.
  11. Processus industriel comprenant un procédé d'émulsification selon l'une quelconque des revendications 1 à 10 en tant qu'étape de processus.
  12. Processus industriel selon la revendication 11, dans lequel ledit processus comprend de plus une ou plusieurs étapes de post-traitement effectuées après l'étape d'émulsification.
  13. Processus industriel selon la revendication 12, dans lequel ladite étape de post-traitement est une étape de séchage pour au moins partiellement enlever le liquide hydrophile présent dans l'étape d'émulsification.
  14. Processus industriel selon l'une quelconque des revendications 11 à 13, dans lequel ledit processus comprend de plus une ou plusieurs étapes pour maîtriser la taille des gouttelettes ou des micelles produites pendant l'étape d'émulsification.
  15. Processus industriel selon la revendication 14, dans lequel ladite étape de maîtrise de taille est effectuée par une analyse dynamique de dispersion de lumière.
  16. Processus industriel selon la revendication 12, dans lequel ladite étape de post-traitement est une étape de sonification.
  17. Procédé d'émulsification selon l'une quelconque des revendications 1 à 10, dans lequel ledit prémélange de deux ou plusieurs liquides non miscibles est du lait, de sorte que la taille moyenne des micelles ou des particules les plus petites contenues dans le lait est diminuée d'au moins 50 %.
EP03776682A 2002-11-14 2003-11-14 Procede de preparation d'emulsions Expired - Lifetime EP1560641B1 (fr)

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GB0226503A GB0226503D0 (en) 2002-11-14 2002-11-14 New emulsification technology
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GB0304356A GB0304356D0 (en) 2003-02-26 2003-02-26 New emulsification technology
PCT/BE2003/000198 WO2004043580A1 (fr) 2002-11-14 2003-11-14 Procede de preparation d'emulsions

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CA2526965C (fr) 2003-05-16 2011-10-11 Velocys Inc. Procede pour former une emulsion par la technique de traitement en microcanal
US7485671B2 (en) 2003-05-16 2009-02-03 Velocys, Inc. Process for forming an emulsion using microchannel process technology
GB0319797D0 (en) * 2003-08-26 2003-09-24 Leuven K U Res & Dev Particle size reduction of poorly soluble drugs
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CN103537211B (zh) * 2013-10-10 2015-07-15 彭伟明 双涡旋体涡旋乳化的方法和装置
CN103537209B (zh) * 2013-10-10 2016-02-17 彭伟明 一种磁场与涡旋相结合的乳化方法及装置
CN103537210B (zh) * 2013-10-10 2015-07-15 彭伟明 一种涡旋乳化方法及装置
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US7629390B2 (en) 2009-12-08
ES2261988T3 (es) 2006-11-16
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MXPA05005132A (es) 2005-08-18
DE60304728D1 (de) 2006-05-24
CA2502908C (fr) 2011-05-10
WO2004043580A1 (fr) 2004-05-27
CA2502908A1 (fr) 2004-05-27
DE60304728T2 (de) 2006-11-16
DK1560641T3 (da) 2006-07-31
US20060040043A1 (en) 2006-02-23
JP2006506229A (ja) 2006-02-23
ATE323547T1 (de) 2006-05-15
AU2003286008A1 (en) 2004-06-03

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